Following the discovery of several molecules by a CSIC research group, Molefy Pharma will become one of the first organizations worldwide to evaluate the viability of this new therapeutic approach.
By Verónica Pavés. Santa Cruz de Tenerife. Originally published by El Día.
A company based in the Canary Islands will lead the clinical trial of a promising new treatment aimed at slowing the progression of amyotrophic lateral sclerosis (ALS). The drug, known as AP-2, represents a breakthrough in the treatment of this neurodegenerative disease, introducing a novel protein-based mechanism of action developed in Spanish laboratories. Preclinical studies have shown its ability to slow down, and even reverse, the disease in patient-derived cells and in animal models.
More than 4,000 ALS patients in Spain
ALS remains a fatal disease. According to the Spanish Society of Neurology, between 4,000 and 4,500 people are currently living with ALS in Spain. The Canary Islands are among the regions with the highest incidence, with around 80 diagnosed patients in Tenerife alone. While approximately 3% of cases have a genetic origin, most are linked to environmental factors. Therapeutic options, however, remain extremely limited.
At present, the only approved drug for ALS is riluzole, which extends life expectancy by just three to six months. This stark reality highlights the urgent need for pharmaceutical innovation and new approaches within biomedical research.
A promising line of research
AP-2 has the potential to radically change this prognosis. “When we tested this molecule in genetically modified mice that develop ALS, cognitive deficits were reversed,” explains Ana Martínez, a chemist at the Spanish National Research Council (CSIC) and principal investigator of the project. Moreover, the effects of AP-2 are enhanced when combined with riluzole.
Martínez has spent decades working alongside fellow researcher Carmen Gil to identify promising molecules for the treatment of neurodegenerative diseases. Their sustained success attracted the attention of ARQUIMEA, a company fully dedicated to R&D, which established a research center in the Canary Islands in 2019.
Among the many compounds studied over the years, AP-2 stands out as one of the most advanced and promising. Its active molecule targets a specific protein mechanism directly linked to the development of ALS.
Mechanism of action
ALS is a multifactorial disease, partly associated with abnormalities in the protein TDP-43. Another protein, CK1, a kinase, plays a critical role by modifying TDP-43 through phosphorylation. This process causes TDP-43 to mislocalize from the neuronal nucleus to the cytoplasm, triggering cellular dysfunction and ultimately neuronal death.
“This incorrect localization and modification lead to progressive cellular failure and death,” explains Mercedes Ruiz, senior researcher at ARQUIMEA. The loss of motor neurons results in the disconnection between the brain and the muscular system, which is the defining clinical feature of ALS.
A new biotech company: Molefy Pharma
Molefy Pharma, a spin-off of the ARQUIMEA Research Center based in Tenerife, will be responsible for validating the drug’s efficacy and ultimately bringing it to market. From its facilities in Las Mantecas (La Laguna), a specialized team is preparing to launch the clinical development program.
The European Medicines Agency (EMA) has already granted AP-2 orphan drug designation, recognizing both its innovative potential and the unmet medical need it addresses.
“This designation provides several advantages, including lower development costs, regulatory support, and ten years of market exclusivity,” explains Ruiz. The company plans to carry out the different phases of the clinical trials between 2026 and 2030.
Clinical trial phases in Spain
Phase I of the clinical trial, focused on assessing safety, is about to begin at Hospital La Paz in Madrid. “We will first recruit healthy volunteers to evaluate safety and then include 28 selected ALS patients within the same phase,” explains Martínez.
If successful, Phase II could begin in 2028, focusing on treatment efficacy. “At that stage, we aim to expand recruitment to patients across Spain,” Martínez adds. Ruiz confirms that this phase will likely involve a multicenter study, including patients from the Canary Islands.
Not all ALS patients will be eligible initially, as strict inclusion criteria are required to ensure scientific validity. Nevertheless, the ultimate goal of this biotechnology-driven, applied research project is to develop a commercially available therapy accessible to all ALS patients.